PA Foundation Annual Report 03

Annual Report 2008

Research Saves Lives

PA Foundation Annual Report02

“As individuals and as a nation, we need to value ideas. The solution to many of today’s challenges will start with an idea and be driven by a commitment to find that solution”

Professor Ian FrazerDeveloper of the Gardasil Vaccine for Cervical CancerAustralian on the Year 2006

PA Foundation Annual Report 03

Over 600 people make up the research staff from Queensland Health and affiliated universities including The University of Queensland, Queensland University of Technology and Griffith University. PA Foundation funded researchers are among the world’s leading medical scientists who are constantly developing breakthrough medications and treatments into areas such as:

• Cancer • Immunology• Transplantation• Diabetes • Cardiovascular disease • Kidney disease• Liver disease • Arthritis • Therapeutics Research

The funds donated to and earned by the PA Foundation are awarded annually to researchers by an independent team of health professionals, clinicians and scientists.

Supporting health and medical research is an ongoing process and a costly undertaking. The PA Foundation receive donations from the general public, community fundraising, business community, bequests and the thousands of patients and their families who have benefited from outstanding medical treatment provided by the PA Hospital. Many hospital staff also donate a percentage of their salary through the foundation’s Workplace Giving Program.

Mission StatementTo raise funds for health and medical research at the Princess Alexandra Hospital Campus for better health outcomes, treatment, prevention and cure of disease.

Vision StatementTo be the forefront provider of funds for collaborative world-class translational research, fostering and sustaining the next generation of science and clinical researchers.

The PA Foundation is a not-for-profit organisation dedicated to financially supporting cutting edge health and medical research conducted on the Princess Alexandra Hospital Campus.

Since its humble beginnings in 1984, the PA Foundation has raised and distributed millions of dollars to research programs that have led to providing better health outcomes, diagnoses and saving lives worldwide.

The PA Foundation 03

Board Members 04 Chairman’s Report 05

Chief Executive Officer’s Report 05

PA Foundation Staff 06

Research Committee 06

Corporate Governance 07

Overview 07

Research Funded in 2008 08

Fundraising in the Community 24

Our Supporters 29

Bequests 29

Financial Report 30

Contents

PA Foundation

PA Foundation Annual Report0404

Mr Michael T Wille OAM Chairman

BA (Hons) Eng, Yale University

Company Director

Mr Michael Back Honorary Solicitor

BA (Hons.) LLB (Hons.)

Managing Partner, Freehills

Mr Phillip SciaccaHonorary Accountant

B.Bus, CA.

Partner, Sciacca & Co, Chartered Accountants

Mrs Linda Lavarch MP Director

LLB, Grad Dip Legal Practice

Member for Kurwongbah

Professor John Prins Director

MBBS, FRACP, PhD

Chair, Research Committee Chair, Centres for Health Research

Mr Gareth Evans Director

BA

Retired newspaper executive

Professor David Theile (Snr) AO Director

MBBS (Hons.) (Qld), MS (Qld), FRACS, FRCS (Eng) FRCS (Ed) (Hons), FANZC (Hons.), FAMS (Hons.)

Clinical CEO, Princess Alexandra Hospital

Ms Heather Tyrrell Board Secretary

Q Health Grad Cert Management

Manager Governance and District Executive Management Services, Queensland Health

PA Foundation Board of Directors

Mr William Deutrom OAM Deputy Chairman

PNA, FAIM, FAICD

Chair, Marketing Committee

Company Director

Mr Richard Bowly Director

AFAMI (Dip.), FAIA, FAIM

Queensland Hotels Association

Dr Richard Ashby Director

MBBS (Qld), BHA (NSW), FRACGP, FACEM, FIFEM, FRACMA

Executive Director of Medical Services, Princess Alexandra Hospital

Professor Ian Frazer Director

BSc (Hons.), MB, ChB, MD

Director, Diamantina Institute

Australian of the Year, 2006

Mr Andrew Griffiths Director

BTRP, MBA, FAIM

Company Director

Ms Lenore Guthrie Director

BN, MHA, Grad Cert Crit. Care, FAIM

PA Foundation Annual Report 05

I would like to thank the Marketing Committee, the Research Committee and the Board of Directors. Your guidance and leadership is as always exemplary. Thank you also to Professor David Theile (Snr) AO and the PA Hospital Executive team for their support and advice.

A special mention also to the PA Hospital staff at Organisational Services and in particular to the Media & Communications team for the help and support given to the foundation on various fundraising and communication activities throughout the hospital.

Last but by no means least, I would like to thank the wonderful staff at the PA Foundation for their passion, dedication and hard work that they continually give day-in day-out. Well done!

Nicholas Allen CEO

As the newly appointed Chief Executive Officer, it is with great pleasure to report on the fundraising activities of the PA Foundation. As we close on another year, we can all stand up and proudly say “we made a difference” to health research conducted on the Princess Alexandra Hospital Campus, based on the significant advancements on various research projects that transpired throughout the year.

Supporting research is a long term commitment for the researchers and scientists as well as for the many people who regularly give to this valuable cause. This is a journey which will lead to new discoveries, as we have seen with the Gardasil® vaccine for cervical cancer.

In appreciation of this support, I am pleased to say that our Recognition Program has been established to acknowledge the generosity and continued support of our loyal donors and corporate supporters, to whom we are so grateful for.

support of the foundation over the years.

For the financial year ending June 2008, the PA Foundation raised and awarded over $1.2 Million dollars including $350,000 from private practice grants. This is an outstanding record amount awarded to our sole objective of financially supporting world class medical research on the Princess Alexandra Hospital Campus.

During the year, our Board accepted the resignation of Ms Lenore Guthrie as the Chief Executive Officer of the foundation. We would like to thank Ms Guthrie for her leadership of the foundation for nearly 3 years, however she retains her role as one of the Directors of the Board.

It is with great pleasure that we welcome Mr Nicholas Allen as our Chief Executive Officer who has been in the position since February 2008. We look forward to supporting him in his efforts to build and manage the foundation and are confident he will provide the level of expertise and leadership vital for our continuing growth and success.

In conclusion, I would like to thank the many corporate and individual supporters who have financially aided our efforts over the past year. Their financial assistance and encouragement have made it all possible.

Michael T. Wille OAM Chairman

This past year has been another eventful year for the PA Foundation as we strive to raise valuable funds for health and medical research conducted at the Princess Alexandra Hospital Campus.

I am pleased to report that the PA Foundation continues to grow with an unprecedented amount of funds available for research to match the increasing number of research applications.

Each year, we invite researchers and scientists on the hospital campus to submit their application for research and/or project grants. These applications undergo a rigorous process and are assessed by the Research Committee.

A special mention must be made to welcome Professor John Prins who has been appointed as the new Chairman of the Research Committee. This is in addition to his responsibility as one of the PA Foundation Board of Directors. Professor Prins has replaced Emeritus Professor Kenneth Donald who recently retired and we would like to take this opportunity to thank Professor Donald for his immense

Chairman’s Report

CEO’s Report

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PA Foundation Staff

Research Committee

E. Professor Kenneth Donald AO Chairman

AO, MBBS, PhD, FRCPA, MRAC Path, FRACMA, FRACS.

Former Head, School of Medicine, University of Queensland.

Professor John Prins

MBBS, PhD, FRACP.

Chair for the Centres of Health Research, Princess Alexandra Hospital.

Head of Metabolic Medicine Program, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland.

Professor of Endocrinology, University of Queensland.

Professor Leanne Aitken

BHSc (Nurs) Hons, PhD, Grad Cert Mgt, Grad Dip ScMed (ClinEpi), FRCNA.

Professor of Critical Care Nursing, Griffith University and Princess Alexandra Hospital.

Professor Thomas Marwick

MBBS, PhD, FACC, FESC, FRACP.

Director of Clinical Centres for Research Excellence, University of Queensland.

Professor of Medicine, University of Queensland.

Professor Ranjeny Thomas

MBBS, MD, FRACP.

Head, Dendritic Cell Biology Group, Diamantina Institute, University of Queensland.

Professor of Medicine, University of Queensland.

Athritis QLD Chair of Rheumatology

Associate Professor Mark Smithers

MBBS, FRCS (Eng), FRACS.

Senior Visiting Medical Officer, Upper GI and Soft Tissue Unit, Princess Alexandra Hospital.

Associate Professor of Surgery, University of Queensland.

Clockwise from top:

Nancy Marinovich Accounts & Administration Officer

Nick Allen Chief Executive Officer

Simone Plunkett Marketing Manager

Tess SiddallCommunications Manager

Jenny Cotter Office Manager

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In 2008, the PA Foundation was proud to have raised and awarded over $1.2 Million dollars including $350,000 from private practice grants. The Princess Alexandra Hospital is one of Australia’s leading teaching and research hospitals, with a strong research culture and active programs in basic science and clinical research. The hospital campus undertakes health research programs independently and with affiliated universities including the University of Queensland, Griffith University and the Queensland University of Technology. Each year the PA Foundation invites applications from health researchers on the campus. Applications are then assessed by the Research Committee, an independent team of qualified medical professionals, and awarded based on merit and funds available.

The philosophy of awarding research grants is to:

• Reward and further promote groups successful in securing competitive funding.

• Attract new researchers to the campus.

• Provide assistance to new researchers in the early stage of their research career.

• Promote the culture of collaboration and group work which is a major strength of the PA research environment.

• All applications are based on scientific quality, relative to the field of research, track record of the researcher or research group and innovation.

Funding Schemes:

• PA Foundation Research/Project grant – for established researchers

• PA Foundation Training grant – for new researchers wishing to undertake research training.

• PA Foundation New Appointment grant – for new appointees to the PAH campus who have an established track record in research.

• Princess Alexandra Hospital Private Practice Trust Fund Research Support grants – these grants are supported by funds from the hospitals private practitioners and administered through the PA Foundation. These grants are exclusively granted to clinician researchers.

• PA Foundation Scholarships – for Allied Health professionals, Registered Nurses, Clinical, Medical and Scientific trainees.

Health ResearchOverview

The PA Foundation is a statutory body incorporated under the Hospital Foundations Act 1982 (QLD). As a statutory body the Foundation is subject to the provisions of the Financial Administration Audit Act 1977 (QLD). The Foundation is audited annually by external auditors representing the Queensland Audit Office and the Auditor General.

The PA Foundation is governed by a voluntary Board which is responsible for the overall strategic direction of the PA Foundation, overseeing its operations and establishing policies and procedures.

The PA Foundation is endorsed by the Australian Taxation Office as an Income Tax Exempt Charity (ITEC) and is a Deductible Gift Recipient (DGR) under the Income Tax Assessment Act 1997 (Cth). It is endorsed for GST concessions under A New Tax System (Goods and Services Tax) Act 1999 (Cth) and it is exempted under the Fringe Benefits Tax Assessment Act 1986 (Cth).

The Role of the BoardThe Board and management have been entrusted with the responsibility of ensuring that monies provided by donors, sponsors and the general public are effectively and efficiently managed.

Board members serve in a voluntary capacity and therefore receive no fees for their services on the Board or Committees.

The role of the Board includes:

• Maintaining high levels of accountability to our stakeholders and external regulators

• Monitoring the performance of the CEO

• Raising organisational awareness of the external environment

• Ensuring compliance with statutory, financial, social and corporate governance responsibilities

• Providing strategic direction and developing, examining and approving strategies, policies, plans and budgets

• Monitoring risk and ensuring the presence of adequate risk management controls and reporting procedures

• Ensuring the Foundation acts legally, ethically, responsibly and openly

Executive ManagementThe Board delegates responsibility for implementing strategies approved by the Board and day-to-day management to the Chief Executive Officer, who in turn is accountable to the Board.

Corporate Governance

Research Committee

PA Foundation Annual Report

Project Title Molecular prognostication in chronic lymphocytic leukaemia.

Project SummaryChronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia in Australia. In most patients, the disease remains stable for many years, whilst in others there is rapid progression with significant morbidity and mortality. Prognosis has been traditionally assessed using the Rai and Binet staging systems which are based on simple clinical and haematological parameters. While these two staging systems can classify patients into broad prognostic groups, they are unable to predict the course of the disease in individual patients, especially in those with early stage disease. The need for good prognostic markers to guide therapy is pressing for several reasons: to provide patients with a clearer picture of their prognosis; to guide follow-up requirements; to enable comparison of results from different clinical trials; and to potentially guide initiation and choice of therapy. This is becoming more important due to the range and intensiveness of treatments becoming available for patients with CLL.

The immunoglobulin variable region gene mutation status and ZAP-70 expression are

powerful biologically relevant prognostic markers in CLL. There are significant limitations in the techniques used to assess these variables that are limiting our ability to use these tests in the clinic. In our study to be performed at the Princess Alexandra Hospital and in collaboration with Associate Professor Collins (an expert in the immunoglobulin protein from the University of New South Wales) we hope to clarify the measurement of these important prognostic variables through the use of new analytical programs and more sensitive and reliable laboratory techniques.

Until these prognostic factors can be reliably assessed, clinical research in CLL is hampered. In addition, their usefulness cannot be brought into the clinic until their measurement can be applied in the routine diagnostic laboratory. We hope that our work will contribute to improved assessment and standardisation of prognostic factors in patients with CLL, better correlation with clinical outcomes, and ultimately better management of patients in the clinic.

AimIn this project we wish to assess two powerful prognostic markers in CLL (ZAP-70 and IgHV mutation status) by using

methodology that is potentially more sensitive and robust, and therefore more reliable. This will hopefully lead to improved clinical application of these important prognostic markers.

The aims of this study are threefold:

1. To determine if use of the iHMMune-align utility and the incorporation of IgHD and IgHJ gene mutations into analysis can improve the assessment of the mutation status of the IgH gene in CLL leading to better correlation with clinical outcome.

2. To investigate whether the ZAP-70 detection method can be improved via the use of RT-PCR to enhance the discriminatory power amongst the different prognostic subgroups of CLL.

3. To determine whether Ki-67 and AnnexinV-Propidium iodide status (after surface IgM stimulation) and Heat shock protein-90 are potential prognostic markers in CLL.

Cancer Collaborative GroupProfessor Devinder Gill Project Funding $100,000

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Project Title The Role of FOXO Transcription Factors in Glucocorticoid-induced Insulin Resistance.

Other InvestigatorsDr Jennifer MoffitDr Janelle BarryDr Louise HutleyDr Charlotte WidbergDr Ayanthi RichardsDr Clair Sullivan

Project SummaryThe general hypothesis is that glucocorticoid-induced insulin resistance occurs through convergence of the glucocorticoid and insulin signalling pathways in the regulation of FOXO proteins and their downstream effectors.

The specific hypotheses are:

Glucocorticoid-induced FOXO1 plays a role in the nucleus by modulating transcriptional effects of metabolically relevant target genes, leading to changes in GLUT4 trafficking to the PM and dysregulation of glucose uptake.

The glucocorticoid-induced increase in cytoplasmic (14-3-3-bound) FOXO1 reduces the amount of 14-3-3 available for interaction with AS160, hence inhibiting GLUT4 trafficking to the PM and glucose uptake.

AimThe overall aim is to characterise the roles of the candidate molecules FOXO1 and 14-3-3 in glucocorticoid-induced insulin resistance.

The specific aims of this study are to investigate the effects of glucocorticoids on:

1. FOXO1 function and expression.2. 14-3-3 expression and binding to relevant interacting proteins.

Significance Glucocorticoids play a well recognised role in the induction and exacerbation of insulin resistance, and they have the most powerful influence on glucose tolerance of any group of drugs in therapeutic use. They are used to

treat a variety of clinical conditions including inflammatory disorders, asthma and as anti- rejection therapy after transplantation. Approximately 40% of individuals administered a supra-physiological steroid dose will have a clinically significant abnormality in glucose homeostasis which may range from mild impairment of fasting or post-prandial blood glucose through to Type 2 Diabetes. Despite the fact that glucocorticoid-induced insulin resistance is a significant clinical problem, the biochemical mechanisms underlying this resistance remain poorly understood. Improved understanding of such mechanisms would firstly provide increased insight into insulin action. In addition, new findings may lead to the development of therapeutic strategies potentially efficacious in both glucocorticoid-induced and other forms of insulin resistance.

Diamantina Institute, Metabolic Research UnitProfessor John Prins Project Funding $30,000

PA Foundation Annual Report

Project TitleResearch in Chronic Respiratory Disease.

Project SummaryChronic obstructive pulmonary disease (also known as COPD or emphysema) is characterised by damage to the air passages and alveoli (air sacs in the lung). The most common cause of COPD in Australia is smoking, while in some parts of the world smoke from cooking fires is also a common cause of COPD. The most effective treatment intervention is avoidance of smoke exposure. While this usually slows the rate of decline in lung function, patients often experience continuing ill health even after stopping smoking due to persisting inflammation in the lung. It is important to understand the mechanisms that cause self-perpetuating lung inflammation in COPD in order to develop new treatment approaches.

COPD patients also seem to be unusually susceptible to viral infections. While many viruses cause only a simple ‘cold’

in healthy people, in COPD patients a minor virus infection can cause a serious deterioration in lung function necessitating hospitalisation. Our studies are examining how the immune system functions in COPD patients, and how this impacts on susceptibility to virus infections.

To date blood samples have been obtained from approximately forty COPD patients and a similar number of healthy people. Methods for culturing rhinovirus, the most common respiratory virus, have been established, and we will shortly commence laboratory studies looking at the effects of rhinovirus on lung cells and blood cells of COPD patients.

With the involvement of Dr Daniel Smith, Respiratory Registrar, we have also commenced a project measuring blood levels of sRAGE, an anti-inflammatory protein. Preliminary data indicates that sRAGE levels are significantly reduced in COPD compared to healthy people. These findings will be presented early next year

at the Thoracic Society of Australia and New Zealand conference. In 2009 we are planning to determine whether sRAGE might be also be involved in the risk of heart disease, a common complication in COPD patients.

Respiratory Medicine, PAH/UQProfessor John UphamProject Funding $50,000

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Project Title Genome-wide Screening for Novel Genetic Lesions in Acute Myeloid Leukaemia. Project SummaryAcute myeloid leukaemia (AML) remains difficult to treat, with relatively poor overall success rates, with 5-year survival rates of 40-50% overall, and as low as 10-20% for some subtypes (see ref.1 and refs. therein). Unlike chronic myeloid leukaemia (CML), AML is a heterogenous group of diseases and there are no molecularly-targeted therapeutics in regular clinical use for this disease. This is partly due to a lack of validated, “druggable” molecular targets in AML. Nevertheless, the success of Imatinib, which targets the underlying oncogenic lesion in CML, in treating this disease highlights the value of identifying and targeting specific molecular lesions. AML is characterised by the continued proliferation and suppressed differentiation of myeloid stem and/or progenitor cells in vivo and frequently in vitro. In the case of human AML, the oncogenic events that

disrupt normal differentiation of these cells and maintain their proliferative capacity have often been identified by their involvement in characteristic chromosomal translocations (reviewed in refs. 2 and 3). However in many cases (up to 50%), the key genes involved in myeloid leukaemias cannot be identified from chromosomal abnormalities as these are either lacking or apparently random1,3. Moreover, even those cases with a known oncogenic translocation or other activating mutation must have additional lesions, since leukaemogenesis requires multiple oncogenic events. Thus there is ample scope for the discovery of additional oncogenic lesions in AML. Achieving this is likely to identify new therapeutic targets, since, as shown by examples such as Imatinib, oncogenes that contribute to leukaemia are excellent candidate drug targets. In this application it is proposed to exploit the power of cutting-edge technologies in cancer genomics to discover additional genes and oncogenic lesions that contribute to AML.

AimOur aim is to identify novel oncogenes and/or tumour suppressor genes that contribute to human AML. This will be achieved by carrying out genome-wide SNP screening on a panel of pathologically-cytogenetically- and clinically-characterised primary AML samples to locate hitherto-unknown regions of genomic gain or loss. This approach has the advantage of being unbiased i.e. it does not rely on assumptions about the nature or identity of putative oncogenes or tumour suppressors.

Diamantina Institute, Cancer Research UnitProfessor Tom GondaProject Funding $100,000

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Project (1) Title NHMRC Senior Principal Research Fellow Fellowship.

Project SummaryThe goal for the next five years is to firstly maintain and grow the current Therapeutics Research Unit (TRU) of ~30 people that I have formed and developed, giving particular emphasis to nurturing the more promising members in the group to seek external funding from NHMRC, ARC, Qld Smart State etc as independent fellows and become CIAs in certain future research grants.

It is also my goal for TRU to increase our translational research in four areas:

1. Applying our expertise to clinically relevant research (60% personal time commitment) as evident by the two new NHMRC grants awarded. Both of which have patient components.

2. Addressing clinical problems at PAH and in the community, in studying antibiotic dosing during cardiovascular bypass surgery, oncology, palliative care and geriatrics therapeutic issues.

3. Integrating basic science, TRU drug delivery/pharmacokinetic expertise and clinical needs to create breakthroughs in diagnosis and treatment (20%), especially in non-invasive and continuous tissue monitoring.

4. Continuing our focus on innovation that can be translated into practice (20% personal time commitment) through direct Industry/ARC Linked and Government funded projects and by reacting to opportunities.

Project (2) Title Targeted delivery by topical application.

Project Summary

HypothesisTargeted delivery by topical application is best achieved by a physiologically based pharmacokinetic, pharmacodynamic and toxicokinetic approach. We lead this project.

AimThe overall aim of this project is to quantify the rate and extent that topically applied solutes and nanotechnologies are absorbed into and retained in human skin and its substructures. Both in vitro and in vivo studies are proposed, using a multiphoton microscope with ethics approval for human studies. Emphasis is placed on quantifying drug and nanotechnology disposition kinetics in 3D space and in time within the skin

Therapeutics Research UnitProfessor Michael RobertsProject Funding $30,000

with a perspective of improving topical therapeutics and minimising potential toxicity after xenobiotic exposure. The various aims relate to uptake, transport in and retention (reservoir effect) in the various substructures of the skin – follicular spaces and furrows in the stratum corneum (aim 1), the stratum corneum (aim 2), viable epidermis (aim 3), hair follicles (aim 4) and diseased skin (aim 5).

SignificanceThis work will examine physiologically-based pharmacokinetics, pharmacodynamics and toxicokinetics at the level of individual substructures in the skin. Importantly, this project addresses therapeutic targeting of specific skin organelles. It also recognises that adverse absorption and effects – for example, immune modulation of Langerhans cells by nanotechnology products – is an emotive human toxicology area. Key aspects affecting these outcomes are the solute chemical structure, formulation and intrinsic toxicity of nanotechnology used in their skin drug delivery. Future animal work in this area is likely to be curtailed with European regulatory initiatives seeking to limit such studies for cosmetic and other products. This emphasises the need to undertake definitive human studies when possible and provides Australia a unique opportunity to lead this important activity.

Project (3) TitleAntibiotic dosing in the “at risk” critically ill patient.

Project Summary

Hypothesis The overall hypothesis for this project is that patients admitted to ICU with severe trauma are undertreated with antibiotics using the current guidelines. Our input is to assay all drugs by LC and LCMSMS, work out pharmacokinetics, derive dosage regimes and write up publications.

Aim Our aim is to identify these patients and, based on their clinical characteristics and applying pharmacokinetic-pharmacodynamic principles, adjust dosing appropriately to maximise their outcomes.

Significance The major concern in ICU is that patients admitted with severe trauma and critical illness without renal dysfunction will receive underdosed antibiotic therapy. This situation is likely to have most significant effect in dosing antibiotics with major changes in renal clearance and/or volume of distribution. Certainly previous research into therapies that

modulate cellular factors in critically ill patients with sepsis have been shown not to be as beneficial as appropriate antibiotic therapy. Given the ongoing high mortality and morbidity of ICU patients, improvement of antibiotic therapy may be a key factor in improving outcomes for these patients.

Project (4) TitleMicronanoprojection patches for minimally invasive and targeted delivery of genes and drugs to skin cells: from concept to technology platform.

Project Summary

AimThis project will address key science questions on the recently patented micro-nanoprojections patch, establishing it is Australia as a world leading technology in the rapidly growing and important field of gene and drug delivery. Unique internationally-competitive science outcomes and research training will be generated at the interfaces between bioengineering, nanotechnology, pharmaceutical science and immunology. Ultimately, the project will allow improved treatment of major diseases (e.g. vaccination and immunotherapy of asthma). Achieving these health benefits by commercial pathways is expected to benefit the Australian community and emerging Biotechnology industry-creating highly valued career opportunities for Australians.

SignificanceSkin epidermal cells have been identified as ideal targets for delivering of genes and drugs, ultimately leading to improved and new health care strategies. However, current delivery methods inadequately deliver to this tightly-defined site. This project aims to investigate and develop a novel biomedical engineering technology we conceived to meet this need, in the form of patches with thousands of micro-nanoprojections-invisible to the human eye-coated with drug and applied to the skin. We will design and fabricate new devices and apply them to in-vitro models and skin to study and optimise their mechanical behaviour, drug coating-release and local immune responses.

Our input is to lead in the drug delivery and pharmaceutical aspects and writing up of papers.

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Project (5) TitleA phase II randomised controlled trial of atorvastatin therapy in intensive care patients with severe sepsis. Project Summary

Aim The major aim of this study is to determine the risk benefit profile of atorvastatin in severe sepsis and to determine the feasibility of conducting a subsequent large phase III study.

SignificanceThis study is a stratified prospective, randomise double-blind, placebo-controlled, phase II trial to assess the effects of atorvastatin on the biological and clinical outcomes of adult intensive care patients with severe sepsis. The study will establish whether a definitive phase III trial in Australia and New Zealand is feasible and justifiable, and will provide essential information on the cost and likely sample size for such a trial.

Our involvement is in (1) Quality assurance and testing of products for administration to patients. (2) Assay of drugs, metabolic and inflammatory markers by LCMSMS, in (3) Pharmacokinetic analysis and (4) Writing manuscripts.

Project (6) TitleModelling of transdermal transport using computational molecular simulation.

Project SummaryTransdermal drug delivery avoids the high waste and variability of oral delivery, and is more practical and acceptable to patients than intravenous delivery. However, despite a wealth of experimental information, links between the physicochemical properties of drugs and their transdermal transport properties remain elusive. Using molecular simulation, we aim to study the transport of a variety of molecules through skin lipid bilayers, which constitute the rate-determining step of transdermal drug delivery. We aim to measure transport properties and identify key mechanisms relevant to transdermal drug transport. An understanding of these transport mechanisms will facilitate the development of more efficient transdermal delivery methods.

Project (7) TitlePharmacokinetics and liver vascularity. AimThis project seeks to understand the impact of liver cirrhosis, fatty liver disease, atherosclerosis, chronic heart failure on liver dysfunction and proposes a number of animal studies as well as human studies to provide insight. The drugs to be studied are those most commonly used in patients with cardiovascular and liver diseases, as one of our main goals is to provide better therapeutic management in these patients. For instance, in patients

who have portal hypertension, it is not certain as to what is the appropriate antihypertensive dose to appropriately lower blood pressure in the presence of changed metabolism of the hypertensive drug.

Significance Better management of liver disease and cardiovascular disease should focus more on the effect of altered hepatic vasculature on drug pharmacokinetics. Cardiovascular and liver diseases represent a major health problem worldwide, with cardiovascular diseases such as atherosclerosis and heart failure accounting for 38% of all deaths in the United States. It is apparent that cardiovascular diseases and primary liver diseases can severely alter the hepatic micro-vascularity and affect hepatic pharmacokinetics. How alterations in the hepatic vasculature affect the disposition of vasoactive drugs is poorly studied. Knowledge of this becomes essential when prescribing vasoactive drugs to patients with cardiovascular disease and associated liver disease, and to patients with primary liver disease. This project addresses the relatively unexplored impact of altered hepatic vascularity on drug disposition. We have a poor understanding of how the effects of these diseases and a number of drugs on liver vessels affect the functioning of the liver, especially in terms of how they affect drug breakdown or removal of drugs.

Our involvement is to lead this project with (a) Studies in liver transplant patients, (b) in perfused rat livers. (c) Conducting assays with LCMSMS. (d) Pharmacokinetic analysis and (e) Writing up of publications.

Project (8) TitleRelationship between melanosome distribution and skin colour.

Project Summary

AimThe project aims to characterize the number, size, melanin content, number and distribution of melanosomes in relation to colour of skin for various races. This will be achieved by a combination of UV microscopy, electron microscopy and confocal microscopy.

The proposed outcome is to be able to predict the colour of skin by changing one of the parameters of the melanosome in the different layers of the epidermis.

Significance The significance of this project is in defining an alternative pharmacological target for modifying the colour of skin that may lead to innovative therapies which maybe better than current approaches such as the use of harsh bleaches, depigmenting agents and damaging UV light.

Project (9) TitleTopical peptide delivery for cosmetic and therapeutic benefits.

Project Summary

AimThis project aims to define rules governing the delivery of peptides (especially those derived from milk) to the different layers of the epidermis using different formulations and certain delivery devices.

SignificanceThe significance of the work is that, although milk has been acknowledged as a good nutrient and is used in skin care formulations, a systematic study of the benefits of milk on the skin has not been carried out. This project will define the distribution patterns of milk peptides in terms of both the properties of the peptides and the delivery systems used.

Project (10) TitleSkin penetration, efficacy and adverse effects of cosmeceutical products used in treatment of skin ageing.

Project Summary

AimIn this project we aim to evaluate the evidence base for the effectiveness of these products. We will measure the amount of active ingredients that penetrate into and through the skin, in live humans, in a mouse grafted with human skin and in excised human skin, using a state of the art multiphoton microscope recently acquired by our unit. This will allow us to see in real time, where these compounds go to in the skin and to look at the biochemical changes that they induce once they reach their destination. In addition, we will document any adverse events produced by topical applications, whether they occur on the skin or systemically, following absorption through the skin.

SignificanceTopical cosmeceutical products are widely promoted to improve skin health and minimize or reverse the effects of skin ageing. Worldwide, the market for these products is growing faster than any other cosmeceutical sector. They are popular because it is generally believed that treatment can delay, or even reverse, the effects of both intrinsic skin ageing (due largely to genetic factors) and extrinsic skin ageing (due to environmental factors such as sunlight or UV exposure and smoking, or poor nutrition). They contain ingredients including Vitamins A, C, D, E or derivatives, hydroxy acids, estrogens, botanical extracts and there is some evidence that for many of these, there is an identifiable biochemical mechanism by which their anti-ageing effects are mediated. However, there is a real lack of objective scientific evidence that the products on the market do actually produce measurable effects on skin.

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Project TitleCCRE in Cardiovascular and Metabolic Diseases, Cardiac MRI sub-study.

Project SummaryThe new CCRE, builds on the successes of the initial CCRE in Cardiovascular and Metabolic Disease. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at understanding the early pathophysiological events in cardiovascular (CV) complications of several “metabolic” conditions and to institute new strategies of exercise and lifestyle intervention to prevent these complications. It will also provide significant opportunities for cross-disciplinary training and career development for clinicians and scientists in clinical research.

Initial results from the initial CCRE, show patients with the most severe metabolic disturbances have the most marked myocardial dysfunction and derive the most benefit from intervention.

This renewal application addresses several important changes in direction:

1. To select for intervention patients with subclinical changes in CV structure and function.

2. To understand the contribution of unexplored mechanisms for CV changes caused by metabolic disease.

3. To initiate a new node to investigate the role of the liver and iron metabolism, and

4. To develop a new, nurse-practitioner- based strategy to deliver a multi- disciplinary, community intervention.

CV changes with obesity were an emerging interest in the initial CCRE.

The goal of this application is to initiate a new collaboration between the CCRE in Cardiovascular and Metabolic Disease, the Diamantina Institute, and the UQ Centre for Magnetic Resonance.

This magnetic resonance program will be added to a trial seeking to limit subclinical myocardial dysfunction using lifestyle change and aldosterone blockade. Preliminary data show improvements of abnormal baseline function with exercise training and aldosterone inhibition. We would like to connect these functional changes with metabolic changes using phosphorus spectra (using phosphocreatine: ATP ratios) as well as proton spectra to investigate fatty acid content of the cells. It is now recognised that intra-cellular fat content is a primary abnormality in cardiovascular disease and the metabolic syndrome. Non-invasive measurement of such fat content in heart, skeletal muscle and liver is crucial for assessment of our subjects at baseline and in response to intervention.

Our primary hypothesis is that the use of an aldosterone blocker can reverse the cardiac changes of obesity by reducing myocardial fibrosis.

Aim1. To correlate echocardiographic evidence of abnormal myocardial function associated with obesity with myocardial fibrosis by MRI.

2. To identify changes in myocardial function and fibrosis in response to anti-fibrotic therapy.

GoalsThe goals of this application are to identify a role for fibrosis and anti-fibrotic therapy in the myocardial disease associated with obesity.

SignificanceHeart failure is associated with obesity and both are reaching epidemic proportions. Understanding the mechanism of preclinical cardiac dysfunction in obesity will enable us to treat this condition before it progresses to causing overt heart failure.

Centre for Clinical Research Excellence (CCRE)Professor Tom Marwick Project Funding $30,000

PA Foundation Annual Report 13

Project TitleStudying the function of antigen experienced CD4+GITR+TC.

Project Summary Cervical cancer is the second most common cancer in women. It is widely known that human papillomavirus (HPV) is the causal agent of genital warts and of cervical cancer, one of the most common causes of cancer death amongst women worldwide.

Aim The aim of the project is to investigate the suppressive function of antigen experienced CD4+GITR+ T cells and identify surface markers unique to antigen experienced CD4+GITR+ T cells.

Antigen experienced and naïve CD4+GITR+ T cells will be purified and incubated with dendritic cells pulsed with VLPs overnight; surface markers on dendritic cells will be checked by FACS analysis. We will check activation markers such as MHC II, CD80 and CD86; surface inhibitory markers such as PD-1, PD-L1 will also be checked.

In another experiment, CD8 T cells from transgenic mice specific with TCR for HPV 16 E7 specific CTL epitope will be added to DC presenting E7 and VLPs /CD4+GITR+ co-cultures. CD8 T cell function will be checked for proliferation, cytokine production and their in vitro killing abilities.

To identify the surface markers of antigen experienced CD4+GITR+ T cells, mice will be immunized with BPVL1 VLPs, on the right side of hind legs intramuscularly on day 0 and 14, draining lymph nodes and control non draining lymph nodes will be collected seven days after final immunization and single cell suspension prepared. The isolated cells will be enriched for CD4 by negative selection using commercially available kit, and then positively selected for GITR. mRNA from CD4+GITR+ T cells either from draining or non draining lymph nodes will be purified and microarray performed at University of Queensland SRC microarray facility. Microarray results will be analyzed by bio-informatics professionals within the institute and special attention will focus on the cytokine activation and

regulation pathway and cell surface gene expression. Gene expression changes of interest will be verified by real time PCR and finally by western blot.

We will study the suppressive function of antigen experienced CD4+GITR+ T cells and try to identify unique surface markers of these cells once the grant is funded. We wish to know through the current project the mechanism of their suppressive function and find pathways that govern the IL10 secretion and identify specific surface markers on these cells.

Diamantina InstituteDr Xiaosung Liu Research Grant $10,000

Project TitlePhase I trial of autologous dendritic cells to induce antigen specific tolerance in patients with rheumatoid arthritis.

Project SummaryIn the current application we seek to purchase equipment required to purify clinical grade monocytes from human peripheral blood. This process, known as elutriation, is based on counterflow centrifugation to isolate cellular subpopulations on the basis of their sedimentation coefficient, a function of cell volume and density. It permits high throughputs in a sterile closed system with excellent recovery of living cells, without the need for antibody or magnetic bead binding of the cells. Recovered cells are suitable for subsequent clinical use, including generation of dendritic cells, as has been previously demonstrated. The JE-6B rotor is capable of speeds necessary for separating the requiredmonocyte fractions from peripheral blood buffy coats, and the standard chamber is suitable for fractionating 2 x 107-1 x 109 cells, after a 250 ml venesection.

Monocytes recovered using elutriation are to be used to generate autologous modified dendritic cells (DC) from rheumatoid arthritis (RA) patients to be administered in a phase I clinical trial of antigen-specific immunotherapy. All other equipment and consumables have been purchased for the trial, and the elutriator will allow us to proceed with a TGA-approved clinical trial.

AimProduction of a quality-assured autologous human cellular product with documented toxicity profile and dose-response, showing capacity for antigen-specific suppression of immunity in vivo, in individuals with RA treated with one or more disease-modifying drugs.

SignificanceWhile current therapies for many autoimmune diseases are often effective in reducing symptoms and disability, these results are often achieved at therisk of side-effects, such as global immune suppression, as well as arequirement to continue treatment long-term if not for life (e.g. anti-TNF a

treatment of RA and insulin for diabetes), and treatment failure in a proportion of patients. There is a recognised need for better treatments with fewer side effects. The technology described here has the potential to overcome many of the problems associated with current treatments. If successful, the current proposal should allow Rheumavax to reach clinical trials to formally test efficacy in disease.

Diamantina InstituteProfessor Ranjeny Thomas Research Grant $10,000

PA Foundation Annual Report

Project TitleDoes Bone Regulate Energy Metabolism in Humans? Evidence from a Clinical Cohort of Obese and Non-Obese Individuals.

Project SummaryIt is well recognised that there is a relationship between weight, bone mineral density (BMD) and fracture risk.The correlation between weight and BMD is around 0.45, and most of this effect is thought to be through fat mass rather than lean mass. Effects of fat upon bone might be exerted through many mechanisms, including load bearing and estrogen production through aromatisation by adipose tissue.

Aim The aim of this study is to test the hypothesis that osteocalcin is involved in negative feedback between the skeleton and adipocytes by determining the relationship between serum osteocalcin, amino-terminal telopeptide of type 1 procollagen (P1NP) [a marker of bone formation and osteoblast activity], fasting glucose, insulin, leptin, and adiponectin; and body composition assessed by dual energy x-ray absorptiometry (DXA), examining both fat and lean mass and bone

mineral density (BMD); in obese and non-obese adults.

Association analysis of bone mineral density and body composition with Osteocalcin, Leptin and Adiponectin will also be undertaken, examining single nucleotide polymorphism (SNPs) and/or haplotypes of these genes in obese and non-obese adults.

SignificanceThe recent publication by Lee et al of the regulation of energy metabolism by the skeleton (Lee, Sowa et al. 2007) has illustrated this critical feedback loop. However, studies in humans are lacking to date, although their potential significance is clearly substantial. This project would be one of the first to examine the relationship of osteocalcin, adipokines and glucose metabolism with body composition measures in humans. The combination in the Department of Endocrinology of researchers and clinicians interested in basic and clinical research in both bone (Dr Emma Duncan) and obesity/type 2 diabetes (Dr Trisha O’Moore-Sullivan), along with state-of-the-art genetics and an already existing cohort of

obese patients places Princess Alexandra Hospital and the Diamantina Institute in a unique position to perform such a project.

The cooperation between the Bone Genetics Group (Dr Emma Duncan); the Clinical Metabolism, Obesity and Diabetes group (Dr Trisha O’Moore-Sullivan), the Department of Biochemistry/ Pathology Queensland Endocrine Laboratories (Dr John Galligan), and the Department of Radiology at Princess Alexandra Hospital (A/Prof Stephen Stuckey) not only makes this project feasible but also would be prime example of collaboration between many individuals and researchers at Princess Alexandra Hospital.

A positive outcome for this study would be likely to lead to publication in high-impact journals, and, more importantly, would provide important background data about the potential of this system as a therapeutic target in obesity, type 2 diabetes, and osteoporosis.

Diamantina InstituteDr Emma DuncanResearch Grant $10,000

Project TitleInvestigation of factors that inhibit Interferon-alpha signalling in chronic hepatitis C.

Project SummaryThere is increasing evidence from clinical studies that hepatitis C virus (HCV)-infected patients with higher body weight have reduced response rates following antiviral therapy, although the mechanisms responsible are not well understood. The underlying hypothesis of this proposal is that cytokines associated with obesity lead to increased insulin resistance, steatosis and increased expression of factors that inhibit interferon-alpha (IFN) signaling. In addition, we hypothesize that peripheral blood mononuclear cells (PBMC) can be used as a surrogate cell population to reflect the effect of metabolic and inflammatory factors on IFN and insulin signaling pathways in the liver. Lastly, we hypothesize that insulin sensitizing agents or modulation of inflammatory pathways can improve response to IFN treatment.

Significance More than 170 million people world-wide are chronically infected with the hepatitis C virus (HCV). Approximately 10-15% of chronically infected subjects develop cirrhosis with its attendant risks of liver failure and hepatocellular carcinoma (HCC). In Australia, the prevalence of chronic HCV is around 1% and the incidence of HCV-related liver failure and HCC is projected to triple by the year 2020 (1). The combination of IFN and ribavirin is the current standard of care for the treatment of chronic HCV. However around 50% of patients infected with HCV fail to achieve sustained viral clearance. Strategies to increase the number of patients achieving a sustained response to antiviral treatment are urgently required. The experiments proposed in this project will show how insulin resistance and other host factors affect the IFN response and will help facilitate the development of additional strategies to increase the effectiveness of antiviral treatment.

Aim The overall goal of this proposal is to delineate the obesity associated factors that inhibit IFN signaling. The effect of obesity on the severity of insulin resistance, oxidative stress and the expression of biomarkers of chronic inflammation in patients with HCV will be determined and whether these factors are associated with the expression of proteins that interfere with IFN signaling eg the suppressor of cytokine signaling (SOCS) family of proteins. The role of selected insulin sensitizing and anti-inflammatory agents on SOCS expression and IFN signaling will be evaluated in human hepatoma cell lines and the Huh7 replicon system with or without insulin resistance and in the presence or absence of steatosis. In addition, the role of PBMC as a surrogate cell population to reflect hepatic IFN and insulin signaling pathways will be determined.

Department of Gastroenterology and HepatologyDr Elizabeth Powell Research Grant $10,000

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PA Foundation Annual Report

Project Title Identification and Characterisation of Cancer Stem Cells in Gastric Cancer.

Project SummaryGastric cancer is the second most common malignancy in the world and continues to carry a poor prognosis. As a result, several experimental protocols using pre-operative chemotherapy or post-operative chemoradiotherapy have been investigated with mixed results. There is a clear need for a better understanding of gastric cancer with respect to both its genesis and progression.

Cancer stem cells represent a self-renewing, tumorigenic subpopulation of cells within gastric cancer that are responsible for tumour progression and metastasis. In addition, the CSCs are may be the source of cells resistant to existing therapies and are responsible for treatment failures. We propose that gastric CSCs can be identified by the expression of stem cell markers and SP analysis

and represent a phenotypically distinct subpopulation of cancer cells responsible for poor clinical outcomes and drug resistance in gastric cancer.

Aim1. To determine the existence of cancer stem cells in human gastric cancer.

2. To establish cultures of human gastric CSCs in vitro.

3. To characterise the gene expression profile of CSCs and non-CSCs in human gastric tumours.

4. To determine the expression of genes involved in stem cell regulation in human gastric cancer, such as hedgehog and CD44.

5. To correlate the expression of stem cell genes with clinical outcomes in gastric cancer in order to determine whether these markers can prospectively identify patients at risk of recurrence.

6. To determine mechanisms of drug resistance in human gastric cancer and

whether gastric CSCs have a differential response to drug therapies compared with the non-CSC population.

7. To determine whether therapies directed against genes involved in stem cell regulation, such as hedgehog and CD44, can inhibit cancer stem cell activity.

Diamantina InstituteDr Andrew Barbour Project Funding $10,000

Centre for Clinical Research Excellence (CCRE)Dr James Sharman Research Grant $10,000

Project TitleEffect of plasma triglycerides on the central haemodynamic response to exercise.

Project SummaryPeople with high blood cholesterol (hypercholesterolaemia) have increased size of the main pumping chamber of the heart (left ventricular hypertrophy), which predisposes them to early death.

In other patient populations, this type of adverse cardiac remodelling is thought to occur due to chronic increases in blood pressure (BP). However, many studies have shown that left ventricular hypertrophy occurs independently of BP in people with hypercholesterolaemia. As such, many research groups have been searching for cellular mechanisms associated with cholesterol to explain the increase in heart size. Interestingly, we recently found that compared to healthy controls, men with high blood cholesterol have significantly raised BP at the heart (central BP) when they exercise at light intensity, similar to activities of daily living. This was found to occur despite no difference from the controls in the BP measured at the traditional site of the upper

arm and, therefore, may help to explain the association between hypercholesterolaemia and increased heart size.

In this current application we aim to elucidate the mechanisms of this abnormal central BP response to exercise in a randomised, placebo-controlled study. This work has potentially important implications relating to early detection and treatment of people at risk of premature death. To our knowledge, there are no other groups in the world exploring this novel hypothesis or utilizing the same techniques to provide an answer for the link between hypercholesterolaemia and left ventricular hypertrophy.

AimThis study aims to determine the physiological mechanisms underlying the abnormal central BP response to exercise in patients with hypercholesterolaemia. Understanding the cause of the abnormal BP response is crucial to the ultimate aim of screening and providing prophylactic treatment to high risk individuals. We have completed two mechanistic studies and the proposed study follows on from these findings.

The first examined the role of nitric oxide, a vasodilatory and cardioprotective molecule known to be depleted in the presence of high blood cholesterol. We found that nitric oxide does not play a significant role in ventricular-vascular interaction during exercise (manuscript under review with Hypertension).

The second study, performed in patients at the PAH, examined the role of plasma viscosity, and found a potential role on exercise wave reflection that may be mediated by raised plasma triglycerides. We now hypothesize that peripheral run off may be impeded in the presence of high plasma triglycerides during exercise, and this will augment arterial wave reflection (AIx) and central SBP, without significant changes to brachial BP. The study proposed in this application will test this and other hypotheses.

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PA Foundation Annual Report16

Project TitleAdiponectin - role in modulating postprandial inflammatory, metabolic and cardiovascular stress.

Project SummaryThe incidence and health care costs of obesity, type 2 diabetes (T2DM) and non-alcoholic-fatty liver disease (NAFLD) are increasing rapidly. Inflammation and oxidative stress are implicated in insulin resistance and cardiovascular disease. Increasing evidence suggests the postprandial state promotes this inflammatory milieu. In addition to the nutrient induced inflammation and oxidative stress, postprandial hyperglycaemia and hyperlipidaemia are associated with endothelial dysfunction and a hypercoagulable state.

Adiponectin, an anti-inflammatory, insulin-sensitising hormone, is synthesised primarily in adipose tissue, and circulates in high levels in various multimeric structures. High molecular weight (HMW) adiponectin appears to be most metabolically active. Hypoadiponectinaemia has been implicated in the pathogenesis of T2DM and NAFLD.

Emerging evidence suggests that postprandial inflammation, oxidative stress and hyperglycaemia alter adiponectin secretion and multimeric distribution.

There is limited and conflicting information regarding postprandial adiponectin levels and, to our knowledge, postprandial adiponectin multimeric distribution has not been evaluated.

Aim 1. To measure baseline and postprandial adiponectin concentration and multimer distribution in the study cohorts.

2. To correlate baseline and postprandial adiponectin profiles with inflammatory and oxidative stress markers, coagulation measures and vascular function in the studied cohorts.

Significance Identifying whether adiponectin may play a role in modulating the response to chronic over-nutrition may help target novel therapeutic avenues, for example, increasing the high molecular weight component of adiponectin.

Diamantina InstituteDr Liza Phillips Training Grant $20,000

Project TitleRole of autonomic neuropathy in diabetic heart disease.

Project SummaryAutonomic dysfunction is an important contributor to subclinical diabetic myocardial disease (DMD) and is responsive to lifestyle intervention.

Aim1. To show an association between DMD and cardiac autonomic dysfunction (demonstrated by nuclear imaging techniques). We also aim to show if these parameters respond to intensive lifestyle interventions designed to improve insulin sensitivity.

2. To show the relationship between DMD and abnormal autonomic function (including cardiac sympathetic innervation) and to initiate a lifestyle intervention program.

SignificanceApproximately 25% of apparently healthy patients with type 2 diabetes (T2DM) have DMD, as evidenced by abnormal tissue Doppler and deformation imaging. This may be an important contributor to the propensity of patients with T2DM to develop heart failure, independent of the role of hypertension and coronary artery disease.

Centre for Clinical Research Excellence (CCRE)Dr Bennett Franjic Training Grant $20,000

PA Foundation Annual Report 17

Project TitleAn assessment of the role of endoplasmic reticulum (ER) stress in the pathogeneses of HCV-related liver injury.

Project SummaryAccumulated evidence from clinical studies indicates that patients with chronic hepatitis C virus (HCV) infection have increased risk for the development of steatosis and insulin resistance, and that obesity, steatosis and type 2 diabetes may have a role in the progression of liver injury.

Recent data from experimental and animal studies show that HCV proteins and obesity may both lead to the development of ER stress. The underlying hypothesis of this study is that in patients with chronic HCV infection, ER stress contributes to steatosis, oxidative stress, NFKB activation and apoptosis, leading to liver injury and impaired insulin signalling. We also hypothesise that in patients with chronic HCV, co-existent obesity will further increase ER stress.

The purpose of the project is to investigate the role of endoplasmic reticulum stress in the pathogenesis of HCV-induced liver injury.

Aim1. To determine the relationship between expression of markers of ER stress and severity of histological features of liver injury (steatosis, inflammation, fibrosis) in patients infected with HCV genotypes 1 or 3.

2. Determine the relationship between host metabolic factors (obesity, type 2 diabetes, insulin resistance) and expression of markers of ER stress in patients with chronic HCV.

3. Examine the mechanisms by which ER stress may contribute to liver injury in patients with chronic HCV. This will involve assessment of the relationship between markers of ER stress and NFKB activation, expression of proinflammatory mediators and markers of oxidative stress.

SignificanceThe underlying pathogenesis of liver injury in HCV infection is largely unknown. A greater understanding of the pathogenesis of HCV related liver injury will enable specific therapies to be developed that may prevent disease progression.

Department of Gastroenterology and HepatologyDr Stuart McPherson Training Grant $20,000

Project TitleAndrogen deficiency in obese men.

Project SummaryAndrogen deficiency (AD) is often associated with poor libido, low energy levels, depression and loss of muscle and bone mass. Interestingly it has been long observed that testosterone levels in obese men are lower than their age matched lean controls. However, current literature is unclear if this biochemical abnormality necessarily translates into true AD. If it is a true condition, most of the existing data suggests that AD is a secondary phenomenon, possibly due to hypothalamic dysfunction. However, there is also evidence that low serum testosterone concentrations predicts future development of obesity, suggesting that relative AD may be a contributing factor for the development of obesity.

As AD alters body composition and contributes to a reduction in absolute and relative lean body mass, the appropriate identification of the condition in obese men may have important clinical implications and sequelae.

Aim 1. To determine if the biochemical abnormalities in the gonadal axis of obese males represent clinically significant AD through:

a. Developing a robust and highly sensitive assay for serum testosterone analysis. b. Assessing the bioactivity of the measured testosterone.

c. Correlating the biochemical levels and functionality of testosterone with reliable clinical measures of androgen status.

2. To determine if anthropometric and metabolic parameters are correlated to AD in obese men.

Centre for Clinical Research Excellence (CCRE)Dr Cynthia OngTraining Grant $20,000

PA Foundation Annual Report18

Project TitlePlacental and adipose tissue inflammatory markers and insulin resistance in normal and obese pregnancy.

Project SummaryIt is recognised that the extremes of size and adiposity at birth are associated with increased rates of coronary heart disease, hypertension and type 2 diabetes mellitus (T2DM) in later adult life. Unfortunately little is known about the precise molecular mechanisms involved in (dys)regulation of fetal growth. Both small and large for gestational age babies suffer an increased risk of later cardiovascular disease.

The consequences of interventions to regulate fetal growth are likely to have lifelong health benefits for the offspring, in particular a reduction in the risk of coronary heart disease and T2DM.

AimBoth placental and adipose tissue inflammation may serve to create an abnormal metabolic state in mother and baby, favouring fat deposition and future adiposity and forming part of the

mechanism of metabolic “programming” in pregnancy. The aim of the project is to examine the relationships between insulin resistance and serum / placental / adipose tissue cellular and cytokine / hormonal profiles in normal and obese pregnant women.

School of MedicineProfessor Harold David McIntyre New Appointment Grant $50,000

Project TitleIdentify Biomarkers to Discriminate Indolent from Aggressive Prostate Cancer and Mechanisms of Therapeutic Resistance.

Project SummaryProstate cancer, already the most common cancer afflicting men in the developed world, becomes increasingly common with advancing age, and based on current incidence rates and aging baby boomers, is estimated to double in incidence and mortality by 2020.

Like most cancers, prostate cancer can progress despite radical local treatments (radiotherapy or surgery) and systemic hormone/chemo-therapy to a lethally resistant stage despite initial encouraging responses. Improved survival will only occur if new therapeutic strategies designed to inhibit the emergence of this resistant phenotype are developed.

Whilst many patients with prostate cancer have a lethal disease a significant group, now detected by widespread use of Prostate Specific Antigen (PSA) testing, have tumours that do not progress. No reliable

markers currently available distinguish between these two extremes of the disease. Consequently many men, who may in fact not require treatment, undergo aggressive therapy resulting in significant morbidity without any improvement in life expectancy. Better biomarkers that add prognostic value need to be identified to clearly stratify patients into those requiring treatment and those that do not need any intervention.

This is even more challenging as prostate cancer typically presents as a multi-focal disease in which tumour foci appear with different genetic lesions that and thereby a given patient harbours different cancer phenotypes. Of patients that require treatment, nearly a quarter will progress to the lethal stage of disease, despite radical local therapy and androgen ablation. We lack an understanding of the mechanisms underlying treatment resistance which will illuminate new therapeutic targets. Thus the two major challenges in the management of prostate cancer are the identification of patients with clinically insignificant disease and the development of an effective systemic therapy for hormone refractory disease.

AimIn this proposal we will address these critical issues in prostate cancer management by comprehensively defining and comparing on a genome-wide scale genetic lesions in prostate cancer specimens using ultra high density array CGH (aCGH) in the following Objectives: 1) Characterize the extent of heterogeneity of multi-focal cancer within a patient by isolating foci from whole mount prostate sections from radical prostatectomies; 2) Compare genetic lesions from prostate cancer patients with clinically significant CaP prior to the PSA era with CaP detected in a contemporary cohort of patients identified by PSA without other clinical features; and 3) Compare genetic signatures of radical prostatectomy patients from PAH with patients that have been treated with androgen ablation or androgen ablation and taxotere prior to radical prostatectomy collected in Vancouver which will illuminate genetic lesions associated with treatment resistance.

Department of Urology, Princess Alexandra Hospital Campus Professor Colleen Nelson New Appointment Grant $50,000

PA Foundation Annual Report 19

Project TitleManagement of patients with malnutrition.

Project SummaryThis research program will investigate a continuum of care for patients with malnutrition, including nutrition screening and assessment, malnutrition coding, and nutrition intervention. Little research has been conducted on these malnutrition issues in Australia, and therefore this research will significantly contribute to the literature in Australia (Ferguson & Capra, 1998).

Objectives1. To conduct a job analysis of the role of nutrition assistants including an evaluation of efficiency and effectiveness (e.g. reducing paperwork and increasing time spent with the patient.

a. To determine nutrition assistants conformity with conducting nutrition screening practices to identify patients at risk of malnutrition.

b. To identify barriers and supportive mechanisms for implementing nutrition screening, and make practice improvements where necessary.

2. To determine the prevalence of malnutrition at the PAH, and its association with other conditions such as falls and pressure ulcers; and outcomes such as length of stay and readmission.

3. To examine whether coding for malnutrition as a comorbidity would have an impact on changing the DRG assigned for the patient’s admission to one with a higher weight and hence, potentially increase the

financial reimbursement to the PAH under casemix funding.

4. To recommend, implement and evaluate a midmeal off trolley select service (nutrition intervention) for patients with malnutrition.

a. To determine if the midmeal trolley system has an impact on clinical outcomes such as length of stay, pressure ulcers and falls.

b. To conduct a cost benefit analysis of the midmeal trolley system including reviewing staff labour time, food consumption and wastage.

c. To assess patient satisfaction with midmeal trolley system.

5. To identify other methods of increasing dietary intake of patients with malnutrition.

Department of Nutrition and DieteticsDr Maree Ferguson New Appointment Grant $50,000

Project TitleHealth status and economic outcomes of critically ill trauma patients.

Project SummaryInjury has consistently been endorsed as a National Priority Area in Australia since 1986 and is a leading cause of preventable mortality and morbidity, particularly among young people. Injury represents a major cost to families, the healthcare system and society.

In Queensland each year more than 12,000 patients are hospitalised for greater than 24 hours for the acute treatment of injury, with more than 10% of these patients requiring admission to intensive care (ICU). The lifetime societal cost of injury in Australia is estimated to be in excess of $13.3 billion per year.

The provision of a cohesive and responsive network of care during and immediately following hospital has the potential to minimise disability, improve recovery and promote cost reduction for this population.

AimThe initial descriptive component of this research will examine the trajectory of recovery, in terms of health and economic outcomes, during two years post-discharge from hospital.

The following hypothesis will then inform the modelling component of this work:

Selected predictors (demography, pre-injury health, socio-economic status, injury characteristics) and moderators (length of stay [LOS], adverse events, psychological status, social support, health service use) have a significant impact on health and economic outcomes over 24 months post hospital discharge in critically injured adults.

While this work will be able to stand alone as an independent piece of research for publication purposes, it will also be used as leverage for NHMRC funding to extend to additional sites to enable assessment of additional site specific factors, e.g. provision of an organised trauma service, ICU liaison nurse service.

Chair, Critical Care Nursing Professor Leanne Aitken New Appointment Grant $50,000

PA Foundation Annual Report20

Cardiothoracic Surgery $50,000Project TitleIdentification of virulence factors expressed by S. aureus during biofilm growth in endocarditis patients.

Investigators• Dr Paul Peters (Chief Investigator)• A/Professor Mark Schembri• Dr Amanda Mabbett

Project AimMolecular analysis of S. aureus induced endocarditis with respect to the human host. The overall aim of this project is to investigate the virulence factors expressed by S. aureus that causes endocarditis in the human host. This will be done under the following two hypotheses and aims.

Hypothesis 1 S. aureus that causes endocarditis expresses distinct virulence profiles when growing on artificial heart valve material.

Aim 1 Transcriptomic and proteomic analysis of S. aureus isolates grown as biofilms in flow-chamber studies on artificial heart valve material. (6 months)

Hypothesis 2 S. aureus that causes endocarditis expresses distinct virulence profiles when growing on heart valves within the human host.

Aim 2 Identification of S. aureus virulence factors expressed during biofilm growth on prosthetic heart valves explanted from patients. (6 months)

Gastroenterology $50,000Project TitleObesity-related inflammation and insulin resistance in chronic liver disease.

Investigators• Dr Graeme Macdonald (Chief Investigator)• Dr Ingrid Hickman• Professor John Prins• Dr Trisha O’Moore-Sullivan

Project AimThe two most prevalent liver diseases in Australia are non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection. Both progress more rapidly in the setting of obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM) however the mechanisms for this relationship with obesity are unclear.

Private Practice Trust Fund Research Support Grants 2008

HypothesisWe hypothesise that 1) visceral adiposity and poor physical capacity contribute to the severity of liver disease through effects on peripheral and hepatic insulin resistance and alterations in serum adipokines and inflammatory modulators, and 2) through an exaggerated post-prandial cytokine response.

This study aims to assess the effect of diet and physical capacity on peripheral and hepatic insulin resistance; and the serum concentration of pro-inflammatory adipokines, and the response of these to a test meal in lean healthy controls and obese patients with histologically proven non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV).

This study will allow us to determine if inflammatory cytokines and the post-prandial response to a meal is associated with disease severity and insulin resistance in patients with chronic liver disease.

Intensive Care $50,000Project TitleApplication for the continuation of funding for a Research Coordinator (RC) position.

Investigators• Professor Bala Venkatesh (Chief Investigator)• Dr. Chris Joyce• Dr. Peter Kruger

Project AimIn 2006, the Department of Intensive Care had applied to the PAH Private Practice Trust Fund for the award of funding to appoint one Full Time RC to the Intensive Care Unit for a three year period to assist in the conduct of a number of locally initiated and national multi-centre trials.

We were successful in securing funding for one year commencing in 2007. This application is to seek extension of this funding for a further two years.

The Research Coordinator (RC) role is to conduct the following studies:

1. Multicentre, prospective, randomised trial of early decompressive craniectomy in patients with severe traumatic brain injury (DECRA).

2. The early nasojejunal tube to meet energy requirements in Intensive Care (ENTERIC).

3. Multicentre, unblinded, randomised, controlled trial to assess the effect of

augmented vs normal continuous renal replacement therapy on 90-day all- cause mortality of Intensive Care Patients with severe acute renal failure (RENAL)

4. Continued use of Atorvastatin in sepsis (CAS)

5. (STATIn) – Prospective multicenter randomised double blind control study of statins in severe sepsis

6. PFCC study – plasma free cortisol sub study as part of STATIns study

Neurosurgery $50,000Project TitleComparing the outcome of open decompression with minimally invasive decompression for symptomatic lumbar canal stenosis: a pilot study. Investigators• Associate Professor Adrian Nowitzke (Chief Investigator)• Dr Martin Wood • Associate Professor Michael Weidmann • Associate Professor Eric Guazzo • Dr Geoff Askin • Dr Owen Williamson

Project AimThe aim of this study is to undertake a randomised pilot study of open laminectomy versus minimally invasive decompression for lumbar canal stenosis to provide information necessary to develop a clinical trial of these two techniques.

The study will examine the techniques in terms of perioperative morbidity and twelve month efficacy.

PA Foundation Annual Report 21

Pathology $50,000Project TitleAn analysis of the Pathological Characteristics of a Proven Epidemiological Cluster of Breast Cancers – ABC Station Patients. Investigators• Dr Glenn Francis (Chief Investigator)• Dr Melissa Brown • Professor Tom Gonda • Dr Nigel McMillan • Associate Professor Nick Saunders • Sandra Stein • Dr Paul Leo • Mark Jones

Project AimA statistically highly significant cluster of 13 breast cancer cases has been documented amongst workers at the former ABC studios in Toowong, Brisbane. The nature and causes of breast cancer clusters remain highly controversial. We therefore wish to test the hypothesis that a common aetiological or contributory factor in such cases may be revealed by detailed pathological and molecular analyses of the breast tumour material form these patients.

Thus our aims are to investigate the histologic, phenotypic and genotypic characteristics that include IHC markers of cell surface receptor molecule expression, oncogenes, tumour suppression genes and metastasis suppression genes in tumours from the ABC breast cancer cluster and to compare these parameters with a subset of sporadic cases of breast cancer occurring in Queensland. In particular, two specific question will need to be answered viz:

1. Are the tumours from the ABC cluster similar to each other at a statistically significant level?

2. Are the tumours from the ABC cluster different of bulk sporadic breast cancers in Queensland i.e. to case matched controls?

Nephrology $50,000Project TitleA Randomised Trial of Intravenous versus Oral Iron Supplements for Post-Transplant Anaemia in Renal Transplant Recipients.

Investigators• Dr David Mudge (Chief Investigator)• Dr Ken-Soon Tan

• Professor David Johnson• Associate Professor Carmel Hawley• Dr Nikky Isbel• Dr Scott Campbell

Project AimPost-transplant anaemia remains a significant problem in renal transplant recipients, and has recently been associated with cardiovascular morbidity and mortality in a large study. Post-transplant anaemia is multi-factorial, but probably contributed to, in part, by iron deficiency.

We have recently noticed that two dialysis patients who received intravenous iron infusions and then coincidentally happened to receive kidney transplants shortly afterwards, maintained normal haemoglobin levels after transplantation.

Oral iron supplements are poorly absorbed and frequently associated with adverse GI effects which limits patients’ compliance with the treatment.

We postulate that a single intravenous iron infusion at the time of transplantation, may ameliorate the post-transplant anaemia, and possibly reduce cardiovascular events in such patients, and seek to test the hypothesis in a randomised controlled trial.

Rheumatology $50,000Project TitleArthritis Complicating Inflammatory Bowel Disease – Prevalence and Genetic Predictors. Investigators• Professor Matthew Brown (Chief Investigator)• Dr Phillip Vecchio • Ms Linda Bradbury • Dr Graham Radford-Smith• Dr Andrew Pascoe Project AimAnkylosing spondylitis (AS) is known to be clinically associated with inflammatory bowel disease (IBD). The prevalence of AS in IBD is not well established, with studies suggesting that between 3-28% of cases have sacroiliitis (1,2), and 10% having clinical AS, compared with a prevalence of AS of 4/1000 in the general community. We and others have previously demonstrated that the major gene for Crohn’s disease, CARD15, is not associated with AS, nor is it associated with IBD complicating AS (3,4). Whether HLA-B27, the major gene for AS, is associated with IBD, has not beenwell studied. We have recently

demonstrated that polymorphisms of IL23R contribute 19% of the population attributable risk of AS (5), and contemporaneously others have established that a similar association exists with IBD (6). We hypothesize that IBD patients that carry disease-associated IL23Rpolymorphisms, either alone or in combination with HLA-B27, are at high risk of AS complicating IBD, and that genetic tests may be of significant diagnostic and prognostic value in determining those IBD cases either with, or at risk of, AS. In the current study we wish to determine the prevalence and pattern of axial spondyloarthritis in IBD, and the predictive and diagnostic value of HLA-B27 and IL23R genetic tests in this setting. We also wish to establish a cohort of IBD cases characterised for arthritisfor future genetic studies.

PA Foundation Annual Report22

Allied HealthAngela Vivanti Project (1) TitleNutritional status, survival and morbidity amongst haemodialysis patients.

Project SummaryRenal disease is a National and Queensland Health priority. Renal disease is one of six diseases attributing to 87.6% of the state’s total burden of disease.

The aim is to determine the effect of nutritional status on outcomes including mortality, morbidity and medication usage in individuals with chronic kidney disease who receive maintenance haemodialysis.

Morbidity and mortality 1. To assess the relationship of mortality and morbidity to predictor variables (including nutritional status and changes in nutritional status).

2. To assess relative risk of the change in scored Malnutrition assessment (PG- SGA score) in predicting mortality.

Nutritional assessments 3. To investigate associations between nutritional status and independent variables including nutrition parameters, hospital admission/readmission and medication usage (eg antibiotics, EPO).

Allied HealthLeanne PassierProject TitlePhysiotherapist observation of cervical alignment in a sitting position.

Project SummaryThis is a sub study of the Acute Brain Injury Physiotherapy Assessment (ABIPA) project which aimed to examine the concurrent validity of visual observation compared to a gold standard and inter-rater reliability of physiotherapist classifications of head and neck positions according to the ABIPA alignment subscale. In determining the validity and reliability of the ABIPA instrument as a whole, individual components of the assessment tool should demonstrate good to excellent clinometric properties individually. Data collection for this study was completed in June 2006, however due to the clinical demands of the investigators further progress has been limited. This funding will provide for time off line to write the paper for publication. One team member is a research fellow who will complete data analysis and provide guidance in the interpretation of results. Specialist rehabilitation services are provided by Princess Alexandra Hospital for patients with brain injury in the Brain Injury Rehabilitation unit and acutely in the Neurosurgical Unit. These patients have a long period of recovery. In the initial phase correct alignment and positioning of body segments influences muscle length, joint range, tonal presentation and overall function. Head alignment is shown to influence overall body postures and is an important initial treatment point. Physiotherapists need to be able to quickly and accurately assess the alignment of head position in order to implement appropriate intervention. In addition to investigating the ABIPA tool this study will provide information about the validity of visual assessment, which is utilised broadly by neurological physiotherapists.

PA Foundation Scholarships

Project (2) TitleScreening of Dehydration in older people admitted to hospital.

Project SummaryA world first, a practical and simple screen with the highest sensitivityand specificity for predicting clinical dehydration has been valiated fromover 130 variables. Support is required to complete publication of results in a timely way after the challenge of completing doctoral studies part-time while working fulltime.

The study aim was to develop a simple, sensitive and robust screen for dehydration (fluid deficit) for use with in older people in the clinicalcare setting. Older people aged 60 years or over admitted to the Geriatric and Rehabilitation Unit (GARU) of two tertiary teaching hospitals were eligible for participation in the study. A large number of potential screening questions were initially tested (n=33) with the most promising selected to undergo final validation (n=86). The most practical and simple screen with the highest sensitivity andspecificity for predicting clinical dehydration assessment was identified.

The screen attained 64% sensitivity and 62% specificity in theidentification of clinically assessed dehydration (fluid deficit). Theresult was not confounded by age, gender or body mass index. Inter-rater repeatability was 70-95%. The screen is a simple, quick, valid and reliable way to identify the dehydration risk of older people in the clinical care setting. The successful development of a screening process for dehydration will identify individuals to undergo further assessment for hydration status. The only dehydration screen identified in the literature was not clinically practical, as it assessed axillary moisture after 24 hours abstinence from antiperspirant use in older people admitted for acute medical conditions (Eaton et al., 1994). The screen’s sensitivity was 50%, positive predictive value was 45% and the inter-rater reproducibility was 80%. Consequently, the study aimed to develop a simple, sensitive and robust dehydration screen for use with older people in the clinical care setting.

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Nursing TravelLinda BradburyProject TitleDisease Outcome in Ankylosing Spondylitis.

Event/Conference6th International Congress on Spondyloarthopathies, October 2-4th 2008.

Project SummaryAs the Ankylosing Spondylitis (AS) specialist nurse, my role involves recruitment of patients and controls for the research programme looking at the genetics of the disease as well as co-ordinating the AS specialist clinic. AS is a common, chronic form of inflammatory arthritis which is classed within a group of diseases known as the Spondyloarthropathies (SpA).

This specialist conference is the major international meeting for SpA, and as such is an ideal opportunity to interact with health care professionals involved in a similar role to my own. As a clinically oriented conference, it is also provides a chance to present our own data from the AS clinic, to share ideas and experiences. As the specialist nurse, I see all newly diagnosed patients for education on the disease process and general health issues such as smoking cessation. I also see those patients with established disease to discuss new treatment options which can include teaching drug administration methods. By attending this conference, there will be an opportunity to discuss current opinions on treatments, their expected outcomes and toxicity as well as views on disease outcome measures.

Aim1. The abstracts I will submit report the findings of studies of patients attending the AS Specialist Clinic at Princess Alexandra Hospital. We are assessing this cohort of patients by using recognised disease outcome measures such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI), and obtaining spinal xrays for quantitative assessment of the extent of radiographic disease using the modified Stoke Ankylosing Spondylitis Severity Score (mSASSS). We wish to test the correlations between the easily administered questionnaire outcome assessments and the more laborious and expensive, but objective score, the mSASSS.

2. A second abstract will be submitted concerning the impact of non-genetic factors on disease-severity, such as smoking, age of symptom onset, socio-economic status, educational level, and presence/absence of associated conditions such as psoriasis/ IBD/uveitis. A third abstract will be presented reporting our experience with TNF-a inhibitors, a relatively new treatment option for AS, assessing response to this medication not only clinically but also from a patient quality of life viewpoint.

Thus, attendance at this conference would provide me with high quality further education relevant to my work as a rheumatology specialist nurse, as well as providing an opportunity to present to an international gathering of AS experts, research findings from patients seen at PAH clinics.

Medical TravelDr James SharmanProject TitleParadoxical Reduction in Pulse Wave Reflection Following Maximal Exercise in Patients with Type 2 Diabetes Mellitus: Association with Exercise Central Blood Pressure.

Event / ConferenceAmerican Heart Association Scientific Meeting - Orlando, Florida, USA.

Project SummaryPatients with type 2 diabetes mellitus (T2DM) have increased large artery stiffness and exaggerated brachial and central systolic blood pressure (SBP) responses to exercise. Elevations in exercise central SBP may be a result of increased arterial wave reflections and this study aimed to test this hypothesis.

AimTo conclude that patients with T2DM have 1) a paradoxical reduction in wave reflection at maximal exercise and 2) a significant inverse association between wave reflection and exercise central SBP that is not observed in controls. The reduced reflected pressure waves may indicate an increase in peripheral vasodilation to offset high exercise central BP.

Medical Travel Matthew HordenProject TitleUse of Diastolic Tissue Velocity and Standard Parameters to Assess Treatment Response in Subclinical Myocardial Disease – A Randomized Controlled Trial of Lifestyle Intervention in Type 2 Diabetes.

Event / ConferenceAmerican Heart Association Scientific Meeting – Orlando, Florida, USA.

Project SummaryMyocardial dysfunction is common in type 2 diabetes (T2DM), but the best markers of treatment response are undefined. We sought the effects of a one year lifestyle intervention (LI) on myocardial function and left ventricular (LV) characteristics, and to determine the predictors of this improvement.

AimTo conclude that Diastolic myocardial properties, but not systolic deformation or standard LV characteristics respond to a one year individualized lifestyle intervention in T2DM. Improved diastolic myocardial function was associated with poor metabolic and myocardial health at baseline and greater improvements in metabolism over the intervention period.

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Smiling for Smiddy Bike Challenge Following the success of the Smiling for Smiddy Ride in 2006, 21 riders took up the challenge in 2007 to raise funds for cancer in memory of Adam Smiddy who passed away from an aggressive cancer at the young age of 26.

The riders and a support crew led by founder Mark Smoothy and Olympic legend Duncan Armstrong, set out to cover the 1600 kilometre journey to Home Hill over eight days, with an average of 200 kilometres per day. A target of $100,000 was set to raise funds for the PA Foundation to go to cancer research at the Princess Alexandra Campus.

Due to the passion and determination of the riders, support crew and sponsors, particularly Bottlemart’s contribution, $193,645 was raised for the PA Foundation to go to cancer research.

A very special thanks to Hitachi who came onboard and contributed an amazing total of $70,000 to kick off the fundraising tally. This was presented prior to the event following the completion of the Gold Coast BRW Corporate Triathlon on Sunday 29 April.

Thank you to all the riders and sponsors that made this achievement possible:

Hitachi Bottlemart Speedwell Rio Tinto Blair Athol Flight CentreAllsports Physiotherapy UQ Sports and University of Queensland Tripleplay 4BC Brisbane The RoomWestfarmers Curragh WotifJacob’s Creek – supplied alcohol (red, white, bubbles) Regatta Hotel – supplied venue Crow Band – supplied their band for free

Sherrin Trust Fund Michael Sherrin sadly lost his wife Helen to an aggressive form of Alzheimer’s disease a few years after she was diagnosed. Helen was looked after by Dr Paul Varghese and his team at the Princess Alexandra Hospital where they worked on trialling new therapies which gave her an extended 18 months of precious time after her initial diagnosis.

As a result of the outstanding treatment and support that Helen and the Sherrin family received during this trying time Michael and his family wanted to set up a fund which would allow Dr Varghese and his team to push forward in their research and help support other families coming to terms with the disease.

The Sherrin Group through a Fundraising Gala Ball raised $150,000 to set up the trust fund at the PA Foundation for Dr Varghese’s work. They also presented another $10,000 cheque to the fund by donating their Christmas gift budget with the full support of their customers and suppliers.

Because of people like Michael and the contributions that they make, one day as Michael says “Alzheimer’s disease will be cured, the answers are out there. We just need to support the researchers and doctors so they can find them.”

Thank you to Michael and the Sherrin Group for supporting this research at the PA Campus.

Fundraising in the Community

Cocktails at the House

Held at the President’s Verandah at Parliament House “Cocktails at the House” was a night to celebrate and pay tribute to two of the PA Foundation’s accomplished female members who have made a positive impact and change in their industries.

Key note speakers Mrs Linda Lavarch MP and director of the PA Foundation and Professor Ranjeny Thomas, PA Foundation research committee member shared their heartfelt stories of juggling families, careers and the challenges and obstacles they overcame on their journey to success.

The evening was largely attended by a female audience representing Brisbane’s corporate world with the aim that they become ambassadors of the PA Foundation to spread the word of the medical breakthroughs women have made in the research world.

May their efforts help us improve the awareness and the significance of research as one of the most important long term investments for the future of all Australian women.

Thank you to Mrs Lavarch and Professor Thomas for their contribution to this successful evening.

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The Great Brisbane Duck Race In 2007 the PA Foundation became the proud organisers and recipients of the Great Brisbane Duck Race, an iconic fundraising event on the Brisbane River as part of the annual RegattaFest day celebrations.

As a result we jumped in with our best fundraising efforts so that on RegattaFest day on September 2nd over 16,500 ducks raced down the Brisbane River in aid of cancer research for the PA Foundation.

PA Foundation supporters, visitors to the hospital and the Brisbane community got behind the race by adopting families, flocks, flushes, flotillas and fleets of ducks!

Following extensive training, the first fit duck over the line was number 10280, winning a Mitsubishi Colt for its owner - Anne of Stafford.

“I am thrilled to have adopted the winning duck and to have contributed to cancer research at the same time!” said Anne when she was presented with her car by Mitsubishi Motors.

The proceeds from the race, including a $20,000 donation from RegattaFest, went towards cancer research at the Princess Alexandra Hospital.

The PA Foundation thanks the generous team at Mitsubishi for the kind donation of a Mitsubishi Colt valued at $23,650 and to the Coles group for taking us onboard and helping raise significant funds for cancer research.

Thank you to our sponsors and suppporters:Coles GroupMitsubishiB105Red PRRegattafestRegatta HotelMaritime Safety QueenslandChannel 7Quest Community NewspapersWorldwide PrintingBowen Tug and BargeWanless Wastecorp

Sommerville House Corporate Luncheon A special luncheon at the Greek Club was held by Sommerville House to highlight the importance of fostering young scientists for the future of health research, with proceeds going to the PA Foundation.

Hosted by our very own Professor Ian Frazer, Sommerville House Old Girl and Channel 9 Newsreader Melissa Downes and Sommerville House students representing today’s aspiring scientists, the luncheon was well attended by a mix of corporate, government and industry representatives.

The luncheon focused on the importance of young scientific researchers in our community and fostering a strong interest in science in schools. Professor Frazer pushed the benefits of promoting science to the younger generation through increased investment from the government and industry to encourage scientific innovation and creativity to ensure the next generation of scientists in Australia.

Thank you to Sommerville House for highlighting the value of science in today’s education for tomorrow’s health research and for giving the proceeds of $1410 for to the PA Foundation for health research.

Hotel Care Week

Hotel Care Week is a partnership between Queensland Hotels Association, PA Foundation and the Mater Foundation. The aim is to raise much-needed funds for our dedicated health and medical research teams, as well as helping regional hospitals.

In the past four years, Hotel Care Week has raised more than $635,000 for this great cause, with every cent raised by hotels donated directly to the PA and Mater Foundations and 13 of Queensland’s regional hospitals.

In 2007 Hotel Care Week raised an impressive $178,000, of which $26,000 benefited regional hospitals and $76,000 was received by each foundation for health research.

A very special thanks to all of the Hotels that put together their own fundraisers in aid of this cause and a thank you to all the sponsors who came onboard. This meant that every dollar raised through the hotelier’s efforts went straight to the hospitals and respective foundations.

Cheers to your good health!

Thank you to our sponsors:

QHA ALH Group LiqourlandMcGuires Group Plainland HotelFitzy’s Fibber Magee Pineapple Hotel

everybody loves a top up!

help top up medical research funds by donating generously.

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Prostate Cancer Awareness Luncheon To help bring prostate cancer awareness to the forefront of men’s health the PA Foundation held the Inaugural Prostate Cancer Awareness Luncheon on Friday 23 May at the Tattersall’s Club. The event was run not only to raise awareness of the disease, but to showcase the groundbreaking research that is being carried out on the PA Campus to help find better diagnosis, treatments and outcomes for prostate cancer sufferers.

Crown Lager and Penfolds wines generously supported the event which was attended by researchers, hospital executives, the local government and the Brisbane business community.

The guest speaker who championed the cause was not only a prostate cancer survivor but our very own Federal Treasurer, The Hon Mr Wayne Swan. Our key note speaker who showcased the latest research into the disease and Head of Prostate Cancer Research at the PA Campus was Professor Colleen Nelson. Thank you to both guest speakers for their compelling personal accounts of the disease and for helping us drive home the importance of ongoing research into this growing epidemic.

The PA Foundation would like to thank all who attended and hope that they will go forth as ambassadors for the cause, building our army to fight this disease.

“A very enjoyable lunch attended by a diverse group of supporters and business people. Not only was the food and company fantastic but the guest speakers inspired me to ensure that I took the threat of prostate cancer seriously.” “Bottlemart and HLW look forward to continuing our support of the PA Foundation… ”

Roy KaufmanGeneral ManagerHotel Liquor Wholesalers

Thank you to our sponsors:Crown LagerPenfolds

Mirvac Construction Charity Golf Day Over 70 Mirvac players and sub contractors joined sports stars Tonie Carroll, from the Broncos, and Aaron Nye and Clinton Perren, both from the Queensland Bulls, for the charity golf day held at Gainsborough Greens in honour of Marty Wickson. Mirvac site Manager Nick Wickson, Marty’s brother, has been organising fundraising events in memory of young Marty since he lost his brother after he suffered an aneurysm in 2004.

This year’s golf day raised more than $25,000 through donations and auctioning off signed Broncos and Queensland Bulls jerseys.

Mirvac Construction Managing Director Geoff Dickens said that he was pleased so many Mirvac staff and sub-contractors had taken part in the golf day and contributed to such a worthwhile cause.

“This is an issue that has impacted on one of our staff members, and indeed many people in our community, so we thought it was important to do our bit to help raise valuable funding for research,” Mr Dickson said.

“We look forward to supporting more events like this in the future”.

Thank you to Marty, Geoff, Mirvac, Koby Slater the organiser, and all the businesses who took part in the event for such a worthy cause.

Other sponsors for the Mirvac Charity Golf Day included: TilecorpTradeLinkBosformWadsworth ConstructionCSRKlenner Murphy ElectricalEd Ahern PlumbingPeer IndustriesHymixCut n CoreJohnston Contracting

Smiddy Fun Run

Over 130 staff members and supporters braved the wet weather on Tuesday 6 November, to take part in the annual Smiddy Fun Run.

The race held in memory of past physiotherapist Adam Smiddy, raised $1,827 for health research through the PA Foundation.

Participants could choose to run the 5km double loop around the PAH campus or walk the shorter 2.5km course.

Run or walk, it was a great way to get active in the morning and socialise with friends over breakfast, while raising money for a good cause.

The winner was Mr Anderson with a time of 17 minutes 36 seconds.

Thank you to all the participants as well as the sponsors, organisers and volunteers who helped out on the day. Next year’s race promises to be even bigger with the introduction of team relays.

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Thank You to all of our Sponsors

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We would like to thank our kind hearted and dedicated volunteers who have donated their time to support us throughout the year. They have helped us tremendously by assisting in fundraising events, running of the PA Foundation’s information booth and providing us with general assistance whenever we needed it the most.

We would also like to acknowledge and thank all of the generous Suncorp Bank and Great Brisbane Duck Race volunteers who donated a day’s work to offer their services at various fundraising events and assisted with general administration duties.

As we do not always have the necessary funds to hire permanent staff for specific events and duties we rely heavily on the members of the community to donate their time to assist us in furthering our cause. We greatly appreciate our volunteer’s time and commitment that they have so generously given to us.

Our Valued VolunteersRay, Yvonne, Dick, Dawn and Karen

The Princess Alexandra Hospital Campus has some of Australia’s most remarkable, world leading medical researchers.

The Workplace Giving Program is an easy and convenient way for our supporters to help bring their medical research to life.

This year, our workplace givers have contributed a total of $24,788 to the PA Foundation directly from their regular wages as a tax deductible donation.

There are over 100 workplace givers from the PA Hospital alone. They have contributed $16,257 and we are confident that this number will continue to grow.

We also thank the generous staff at The Southern Hotel in Toowoomba and Australian Leisure and Hospitality Group (ALH) for their contribution of $8,531.

Donations for the Workplace Giving Program are received free of cost to the PA Foundation. This means 100% of the donations received goes directly to health and medical research.

Workplace Giving Program

PA Foundation Annual Report 29

Gifts made through a Will may include the whole of or a portion of an estate, a specific amount of money or the residual of the estate. These gifts may also include real estate, stocks and shares, works of art or any other asset.

A bequest may also be specific in its wording nominating a research program such as heart, prostate cancer, spinal injury etc. All these options are covered in our bequest information which is available on request.

Our Free Will program is available to anyone who wishes to include the PA Foundation as a beneficiary of their Estate and does not have a current or up to date Will. We will introduce the Testator to a solicitor with whom we have an arrangement, who will take instruction and prepare the Will at no cost to the Testator.There is no set amount for the bequest, as a requirement to participate in the Free Will program. Even a modest amount will be well received with gratitude and sincere thanks.

For more information contact:

Cheif Executive Officer, Nicholas Allen on 07 3240 7301 or email nicholas_allen@health.qld.gov.au

Bequests andFree Will

Donations$10,000 + Mr & Mrs Peter IslesMr John Savoy

$5,000 - $10,000Mr Matthew PercyMr Cecil McMillan

$1,001 - $4,999Mrs E PiotrowskiMr Trevor WilliamsMr Ellis SchmutterMrs J GoslingMr & Mrs Josh SimmonsMrs Heather JordanMr Richard JaworskiMs Elizabeth MacPhersonMr Maurice MillsomMr Ivan BignillMr David Laing

$1,000Mr C R ActonMs Jessica ChouMr & Mrs U D’AlessandroMr & Mrs Stanley Fraser

Ms Kerry LawfordMr & Mrs Bob KennedyMr Steven BatemanMiss Sandra BekavacMr Bruce BoltonMr & Mrs Anthony HennMr Paul O’BrienMr David SilvestriMrs Riitta VahlmanMr Peter Wade

Community$10,000+Sherrin Group Pty LtdColes Group

$1,000 - $4,999Jones Lang LaSalle HotelsZonta Club of RomaQueensland Country Women’s AssociationSomerville House

$1,000Bec Feed Solutions Pty LtdGRS Mechanical Pty LtdRotary Club of Blackwater

BequestsEstate of Mary O’Keefe Charitable Trust

Our Supporters

For a copy of the Financial Statements, please call 07 3240 2359 or visit www.pafoundation.org.au

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PA Foundation Annual Report02

ANNUAL REPORT 2008

Princess Alexandra HospitalBuilding 15, 199 Ipswich RoadWOOLLOONGABBA QLD 4102

Telephone 07 3240 2359Facsimile 07 3240 7303

Email general@pafoundation.org.auwww.pafoundation.org.au